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Receptor-mediated Uptake of Folic Acid-functionalized Dextran Nanoparticles for Applications in Photodynamic Therapy

1
Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudingerweg 5, 55128 Mainz, Germany
2
Department of Health Technology, Technical University of Denmark, Produktionstorvet Building 423, 2800 Lyngby, Denmark
3
School of Chemical Engineering, University of New South Wales, Science and Engineering Building, Sydney, NSW 2052, Australia
4
Australian Centre for NanoMedicine, University of New South Wales, Sydney, NSW 2052, Australia
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Polymers 2019, 11(5), 896; https://doi.org/10.3390/polym11050896
Received: 3 April 2019 / Revised: 30 April 2019 / Accepted: 10 May 2019 / Published: 16 May 2019
(This article belongs to the Special Issue Polymeric Nanoparticles for Drug Delivery and Diagnostics)
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Abstract

In photodynamic therapy (PDT), photosensitizers and light are used to cause photochemically induced cell death. The selectivity and the effectiveness of the phototoxicity in cancer can be increased by a specific uptake of the photosensitizer into tumor cells. A promising target for this goal is the folic acid receptor α (FRα), which is overexpressed on the surface of many tumor cells and mediates an endocytotic uptake. Here, we describe a polysaccharide-based nanoparticle system suitable for targeted uptake and its photochemical and photobiological characterization. The photosensitizer 5, 10, 15, 20-tetraphenyl-21H, 23H-porphyrine (TPP) was encapsulated in spermine- and acetal-modified dextran (SpAcDex) nanoparticles and conjugated with folic acid (FA) on the surface [SpAcDex(TPP)-FA]. The particles are successfully taken up by human HeLa-KB cells, and a light-induced cytotoxicity is observable. An excess of free folate as the competitor for the FRα-mediated uptake inhibits the phototoxicity. In conclusion, folate-modified SpAcDex particles are a promising drug delivery system for a tumor cell targeted photodynamic therapy. View Full-Text
Keywords: nanoparticles; dextran; targeting; folic acid; photodynamic therapy nanoparticles; dextran; targeting; folic acid; photodynamic therapy
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Butzbach, K.; Konhäuser, M.; Fach, M.; Bamberger, D.N.; Breitenbach, B.; Epe, B.; Wich, P.R. Receptor-mediated Uptake of Folic Acid-functionalized Dextran Nanoparticles for Applications in Photodynamic Therapy. Polymers 2019, 11, 896.

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